The anatomical subdivision of striatum in patch and matrix compartments plays an important role for the processing of neurotransmission through the basal ganglia in primates and rodents. Here we report that co-administration of D₁/D₅ and D₂ receptor agonists, which induces a heterogenous and patchy pattern of c-fos messenger RNA expression in striatum, stimulates c-fos messenger RNA expression in cholinergic interneurons. Moreover, this treatment induces c-fos messenger RNA in projection neurons containing D₁-, rather than D₂-receptor messenger RNA. The preferential induction of c-fos messenger RNA in patches does not depend upon a higher degree of co-localization between D₁ and D₂ receptors in this area, since double in situ hybridization experiments showed a large segregation of D₁ and D₂ receptor messenger RNAs in the patch as well as the matrix compartments. By contrast, treatment with a full D₁/D₅ receptor agonist up-regulates striatal c-fos messenger RNA homogenously and in similar proportions of D₁ and D₂ receptor messenger RNA-containing projection neurons in both medial and lateral striatum, but has only minor effects on c-fos messenger RNA expression in cholinergic interneurons. These results provide a neuroanatomical/neurochemical correlate to the well-known behavioral interaction between dopamine D₁/D₅ agonists and dopamine D₂ agonists. They also suggest that there may be a relation between a heterogenous, patch-enriched c-fos messenger RNA expression and an increased expression of this immediate early gene in cholinergic interneurons.